The goal of this project is to investigate the mechanisms which are responsible for the movement of water and of various solutes across epithelial tissues. Epithelial cell layers will be mounted in appropriate chambers to study in vitro phenomena which are connected with transport across epithelia. Measurement of transepithelial potential and current as well as determination of transepithelial unidirectional fluxes of sodium, chloride, choline, potassium and of non-electrolytes of various molecular weights will be carried out under conditions in which the composition of the bathing solutions is changed by altering systematically the concentration of different anions and cations. These experiments will provide new information about the factors which control transepithelial transport. In another study, potentials and currents will be measured by intracellularly located microelectrodes and, in part, analyzed by computer in order to obtain information about the mode of transfer of ions across the cell membranes on each (apical and basolateral) side of the epithelial cells. Also in this study the epithelial tissue will be studied under different conditions which change the rate of support at various sites of the transport pathways. Special attention will be given to the action of metabolic inhibitors, drugs (diuretics, for example) and hormones.